Thesis

Preliminary investigation of glutamine transporter SLC7A8 role in mediating cuproptosis in patient-derived primary glioblastoma cell

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Glioblastoma multiforme (GBM) is a highly aggressive glioma that is reported to exhibit elevated
glutamine uptake and metabolism, termed as glutamine addiction, often associated with poor patient
prognosis. Recently, a preliminary study identified glutamine transporter SLC7A8 to be highly
upregulated in resistant GBM and associated with poor prognosis, with results intriguingly showing
distinct responses between wild-type and resistant GBM upon SLC7A8 knockdown where increased
viability was instead observed in the former. Cuproptosis is a recently discovered cell death mediated
by the intracellular accumulation of copper ions upon elesclomol treatment. The current study aims to
evaluate the role of SLC7A8 in patient-derived primary GBM cell line Pt#3 and explore its role in
mediating cuproptosis through its effects towards cuproptosis markers, as well as other pathways. The
current findings confirmed that SLC7A8 knockdown increased the viability of Pt#3 cells. Remarkably,
its knockdown concurrently increased the cells’ sensitivity towards cuproptosis. While the exact
mechanisms remain to be further elucidated, the results suggest that SLC7A8 indirectly mediate
cuproptosis through promoting the TCA cycle and regulating intracellular copper transporters and
chelators. SLC7A8 was also high associated with the immune responses in GBM in silico. Collectively,
these findings suggests the prospects of inducing cuproptosis upon SLC7A8 knockdown as a novel
therapeutic approach in GBM.

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Availability

Detail Information

Series Title

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Call Number

BM 24-041

Publisher

i3L, Jakarta : i3L Press., 2024

Collation

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Language

English

ISBN/ISSN

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Classification

NONE

Content Type

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Media Type

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Carrier Type

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Edition

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Subject(s)

glioblastoma multiforme
glutamine addiction
SLC7A8
cuproptosis

Specific Detail Info

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Statement of Responsibility

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